Structure-activity relationship studies of lipophilic teicoplanin pseudoaglycon derivatives as new anti-influenza virus agents

European Journal of Medicinal Chemistry
Zsolt SzűcsAnikó Borbás

Abstract

Six series of semisynthetic lipophilic glycopeptide antibiotic derivatives were evaluated for in vitro activity against influenza A and B viruses. The new teicoplanin pseudoaglycon-derived lipoglycopeptides were prepared by coupling one or two side chains to the N-terminus of the glycopeptide core, using various conjugation methods. Three series of derivatives bearing two lipophilic groups were synthesized by attaching bis-alkylthio maleimides directly or through linkers of different lengths to the glycopeptide. Access to the fourth and fifth series of compounds was achieved by click chemistry, introducing single alkyl/aryl chains directly or through a tetraethylene glycol linker to the same position. A sixth group of semisynthetic derivatives was obtained by sulfonylation of the N-terminus. Of the 42 lipophilic teicoplanin pseudoaglycon derivatives tested, about half showed broad activity against influenza A and B viruses, with some of them having reasonable or no cytotoxicity. Minor differences in the side chain length as well as lipophilicity appeared to have significant impact on antiviral activity and cytotoxicity. Several lipoglycopeptides were also found to be active against human coronavirus.

Citations

Jul 12, 2020·ChemMedChem·Ilona BereczkiPál Herczegh
May 27, 2020·International Journal of Antimicrobial Agents·Giancarlo CeccarelliUNKNOWN Intensive Care COVID-19 Study Group of Sapienza University
Mar 17, 2020·Journal of Microbiology, Immunology, and Infection = Wei Mian Yu Gan Ran Za Zhi·Chih-Cheng LaiPo-Ren Hsueh
Jun 13, 2021·Food and Chemical Toxicology : an International Journal Published for the British Industrial Biological Research Association·Shivraj Hariram NileGuoyin Kai
Dec 9, 2021·ACS Infectious Diseases·Yash AcharyaJayanta Haldar

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Methods Mentioned

BETA
column chromatography
silica gel chromatography
Assay
flow cytometry

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